Processes and methods of manufacture of arecoline

ABSTRACT

Processes and methods of manufacturing an areca fruit product. One process may include the steps of providing a plurality of areca fruits, drying the plurality of areca fruits, dehusking the plurality of areca fruits to obtain a plurality of areca nuts, chopping, shredding or grinding the plurality of areca nuts into a multiplicity of areca nut particles, introducing the multiplicity of areca nut particles into a tank containing water, agitating the multiplicity of areca nut particles to create a slurry, determining an amount of arecoline in the slurry and pumping the water having the predetermined amount of arecoline through a filter and into a holding tank and concentrating the arecoline in an evaporator. Additional steps include fermentation, distillation, pasteurization, and cold pressing of the arecoline to produce a synthetic nicotine and/or botanical pesticide.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.13/999,650, dated Mar. 15, 2014, which claims priority to U.S.Provisional Application Ser. No. 61/852,401, filed Mar. 15, 2013.

DETAILED DESCRIPTION OF THE INVENTION

In the following description, for the purposes of explanation, numerousspecific details are set forth in order to provide a thoroughunderstanding of the synthetic or imitation nicotine of the presentinvention. It will be apparent, however, to one skilled in the art thatthe synthetic or imitation nicotine may be practiced without some ofthese specific details. Throughout this description, the embodiments andexamples shown should be considered as exemplars, rather than aslimitations on the synthetic or imitation nicotine. That is, thefollowing description provides examples, and the accompanying drawingsshow various examples for the purposes of illustration. However, theseexamples should not be construed in a limiting sense as they are merelyintended to provide examples of the synthetic or imitation nicotinerather than to provide an exhaustive list of all possibleimplementations of the synthetic or imitation nicotine.

Specific embodiments of the invention will now be further described bythe following, non-limiting examples which will serve to illustratevarious features. The examples are intended merely to facilitate anunderstanding of ways in which the invention may be practiced and tofurther enable those of skill in the art to practice the invention.Accordingly, the examples should not be construed as limiting the scopeof the invention. In addition, reference throughout this specificationto “one embodiment” or “an embodiment” means that a particular feature,structure or characteristic described in connection with the embodimentis included in at least one embodiment of the present invention. Thus,appearances of the phrases “in one embodiment” or “in an embodiment” invarious places throughout this specification are not necessarily allreferring to the same embodiment. Furthermore, the particular features,structures or characteristics may be combined in any suitable manner inone or more embodiments.

The social taboo of smoking nicotine-containing products likecigarettes, cigars, pipes and the like continues to increase. However,individuals may wish to continue to enjoy nicotine. The presentinvention provides compositions, mixtures, and methods of manufacturefor a synthetic or imitation nicotine. Embodiments of the presentinvention provide tobacco flavor, and/or transmit nicotine or othermedical preparations that add to the enrichment and/or safety of vaporpassing through the mouthpiece end of an electric (or other powersource), cigarette, electric cigar, or any vaporizing apparatus.

Generally, nicotinic receptors are integral membrane proteins thatrespond specifically to receptors involved in the regulation of avariety of physiological and behavioral functions including memory,cognition, respiration, concentration etc. Such correlations suggestthat nicotine and its analogs which modulate nicotinic acetylcholinereceptors that are mimicked into our synthetic or imitation nicotinewill have beneficial effects for discouraging the urge to use nicotine.

Though only certain types of these receptors are associated withaddiction, nicotine activates all of them non-selectively and may causedependency after long term use. However, nicotine's well-known potentialfor abuse and toxic effects on the gastrointestinal and cardiovascularsystems prevent its use as a drug. Development of a synthetic orimitation compound based on the core nicotine structure, without theseside effects, has been limited by the lack of methods for preparingsynthetic or imitation derivatives from naturally available nicotine.Thus, there is a need to develop methods for synthesis of nicotineanalogs with receptor-type selectivity for safe and effectivereplacement of nicotine.

One nicotine analog that may he employed by the present inventioncomprises arecoline, an alkaloid found in the areca nut (also known asbetel nut), the fruit of the areca palm (Areca catechu). The areca nutscontain at least nine (9) structurally related pyridine alkaloids,including arecoline, arecaidine, arecaine, arecolidine, guvacine,isoguvacine, guvacoline, and coniine However, the most common is theparasympathetic stimulant alkaloid arecoline. The total alkaloid contentcan reach 0.45%.

The areca palm grows in much of the tropical Pacific, Asia, and parts ofeast Africa. It is commonly referred to as betel nut, as it is oftenchewed wrapped in betel leaves. The areca nut is not a true nut, butrather a drupe. It is commercially available in dried, cured and freshforms. While fresh, the husk is green and the nut inside is soft enoughto be cut with a typical knife. In the ripe fruit, the husk becomesyellow or orange and, as it dries, the fruit inside hardens to awood-like consistency. Usually consumed by chewing, a few slices of thenut are wrapped in a betel leaf along with lime (not to be confused withthe citrus fruit named lime) and may include clove, cardamom, catechu(kattha) and/or other spices for extra flavoring. Betel leaf has afresh, peppery taste, but it can also be bitter to varying degreesdepending on the variety.

Arecoline is a strong base, with pKa—6.8. Arecoline is volatile insteam, miscible with most organic solvents and water, but extractablefrom the latter by ether in presence of dissolved salts. Being basic,arecoline forms salts with acids. The salts are crystalline, but usuallydeliquescent: the hydrochloride, arecoline-CI; the hydrobromide,arecoline-Br; and the urichloride, arecoline-AuC14.

Arecoline is the primary active ingredient responsible for the centralnervous system effects of the areca nut. Arecoline has been compared tonicotine; however, nicotine acts primarily on the nicotinicacetylcholine receptor. Arecoline is known to be a partial agonist ofuscarinic acetylcholine M1, M2, M3 receptors and M4, which is believedto be the primary cause of its parasympathetic effects (such aspupillary constriction, bronchial constriction, etc.). These centralnervous system effects on humans may also have analogous functions ininsects and other pests whereby the arecoline can function as a naturalbotanical pesticide.

Basic ingredients employed in the arecoline product of the presentinvention may be used alone or in combination with other additives aredistilled or manipulated to insure conformity to health standards. Theseingredients can be applied after extracting from organics n a solid,powder or liquid form in a concentrate or a tincture, oil or in anotherbase.

Embodiments of the present invention comprise novel processes thatinvolve producing synthetic or imitation nicotine from naturallyoccurring chemical compounds, such as arecoline. Other substancescontained include, but are not limited to: vegetable-glycol (VG),lycerin, poly-glycol (PG), tannin, gallic acid, nipecotic acid, a fixedoil gum, terpineol, lignin, various saline substances and up to five (5)alkaloids.

For example, one method of practicing the present invention comprises aprocess of preparing an areca fruit, the process comprising the steps ofproviding a plurality of areca fruits, drying the plurality of arecafruits, dehusking the plurality of areca fruits to obtain a purality ofareca nuts, chopping, shredding or grinding the plurality of areca nutsinto a multiplicity of areca nut particles, with a mean particle size ofbetween 300-5000 microns, immersing the multiplicity of areca nutparticles in a water filled tank to create a slurry and extracting anarecoline from the slurry.

The slurry is recycled through the water filled tank as additionalmultiplicities of areca nut particles are added to the water filled tankuntil an arecoline concentration in the water reaches a predeterminedamount and pumping the water having the predetermined amount ofarecoline through a filter and into a holding tank. The water having thepredetermined amount of arecoline is transferred from the holding tankinto an evaporator and the arecoline is concentrated in the evaporator.The concentrated arecoline is transferred to a spray drier, and thearecoline is collected from the spray drier in a dry powder form.

One embodiment of imitation nicotine of the present invention comprisesevaporating the arecoline to a solid content that may range between 10%and 90%, but other percentages may also be employed. The arecoline ismixed with another element which may be any one of: an alcohol, a water,a vegetable glycol, a glycerin, a poly-glycol, and a combination of twoor more thereof.

Another method of practicing the present invention comprises a processof preparing an areca fruit, the process comprising the steps ofproviding a plurality of areca fruits, drying the plurality of arecafruits, dehusking the plurality of areca fruits to obtain a plurality ofareca nuts, chopping, shredding or grinding the plurality of areca nutsinto a multiplicity of areca nut particles, introducing the multiplicityof areca nut particles into a tank containing a mixture comprising waterat a temperature between 40-90° Centigrade and a pH adjusted to a rangebetween 4.0 and 8.0, and adding at least one element, the elementselected from a group consisting of: a sulfuric acid, a salt, an organicsolvent, an ether, and a combination of two or more thereof. The mixtureis then agitated to create a slurry, and an amount, or percentage ofarecoline in the slurry is determined. Additional multiplicities ofareca nut particles may be added to the tank until an arecolineconcentration in the tank reaches a desired amount and then the waterhaving the predetermined amount of arecoline is pumped through a filterthat removes all, or most of the areca nut particles. The water is thenintroduced to an evaporator that concentrates the arecoline. Ifnecessary, a spray drier may also be employed until the arecoline is ina dry powder form. Once in a dry powder from, the arecoline may be usedin an imitation nicotine product of the present invention.

In other embodiments, one method of practicing the present inventioncomprises a process of preparing an areca fruit, the process comprisingthe steps of providing a plurality of areca fruits, drying the pluralityof areca fruits, dehusking the plurality of areca fruits to obtain apurality of areca nuts, chopping, shredding or grinding the plurality ofareca nuts into a multiplicity of areca nut particles, with an exemplarymean particle size of between 300-5000 microns, immersing themultiplicity of areca nut particles in a water filled tank to create aslurry. Extraction and preparation of arecoline may be accomplished bymethods complimentary to or in substitution for theevaporation/concentration methods heretofore disclosed, for example,methods of fermentation, pasteurization, distillation, and/or coldpressing processes may be employed to obtain a final arecoline product.

Fermentation can be included into this process and can be carried out ina variety of ways inside a sealed container that has qualities thatallow for the expulsion of gasses that may develop, but all methodsdepend on placing the slurry in a solution, for example a water-basedsolution, that allow micro-organisms to develop and initiate thefermentation. The process requires growth of micro-organisms whereproducts like yeasts are added to the slurry. The yeasts convert anysugars present in the arecoline slurry to produce ethanol. Complexchemical changes take place with the slurry producing a reaction ofbreakdown of proteins, enzyme activity, and/or oxidation resulting inamino acids. Following fermentation of the arecoline slurry,nonessential elements of the resultant fermented arecoline is filter toobtain a purer final product. In some embodiment, the fermentation stepcan occur after the concentration step in the above methods, wherebyconcentrated arecoline is reprocessed into a slurry and later fermented.This allows the desired quantities and final quality of the arecolineproduct to be specified more readily.

A pasteurization process may also be put into operation at slurry stageor as a secondary step following concentration of the arecoline asdescribed above. The process of pasteurization is accomplished byincreasing the temperature of the slurry solution high enough to destroyor significantly reduce the number of viable pathogens, such asbacteria, so they are unlikely to cause disease and inactivate mostenzymes that cause spoilage. This can be done in temperature safecontainers where the temperature can be safely increased to the currentlevel required to establish pasteurization. Pasteurization methods areusually standardized and controlled by national food safety agencies butmost require that the slurry is heated to at least 72° C. for at least16 seconds then cooling it to 4° C. to ensure any harmful bacteria aredestroyed. Pasteurization can greatly increase the sterility andshelf-life of the resultant arecoline product, providing a safer andmore marketable final product.

Distillation of the slurry can also be added as step at the slurry stageor as a secondary step following concentration of arecoline. In someembodiments, the slurry or concentrated arecoline is purified byprecipitating and collecting the hot vapors coming off the boilingslurry or re-wetted arecoline solution are collected. Both atmosphericand vacuum distillation methods can be employed but vacuum methods areparticularly useful after distilling the slurry at atmospheric pressure.Vacuum distallation requires a lower boiling point that therebyeliminates heat that could facilitate unwanted chemical reactions withinthe arecoline slurry or concentrate or that would otherwise combustuseful and active elements of the arecoline.

Cold pressing of the slurry or the concentrated arecoline can also beincorporated as an additional method step. Cold pressing offers theadvantage of eliminating heat and producing a concentrate that has beenfiltered while being pressed. The slurry or arecoline concentrate isplaced into an industrial filter bag and then is compressed allowing theparticulate matter to be eliminated resulting in a cold-pressed arecafruit product or concentrated pressed product free from organic solids.This product has a more uniform resultant product that can beincorporated into admixtures and formulated for uses where it isundesirable to have solid particulate matter.

The arecoline final product produce in accordance with the variousembodiments of the present methodology may be mixed with anotherelement, the element selected from a group consisting of: an alcohol, awater, a vegetable glycol, a glycerin, a poly-glycol, and a combinationof two or more thereof. This mixture may be sprayed on a material andthe material may be flavored with a tobacco or a menthol flavor.Alternatively, the mixture may be kept in a liquid form and used in anelectronic cigarette, vaporizer or other apparatus.

That is, the imitation nicotine can be delivered in a powder or liquidform with varying percentages of active base obtained by addition orsubtraction of non-active organics or matter. Potency can be easilyregulated by volume. When the arecoline is distilled to a 16% level ofconcentration or more and added to vegetable-glycol (VG) or, glycerin orpoly-glycol (PG), this tincture mixture can produce a working imitationnicotine product that can be used in electric vapor units. Any desiredconcentration of volatile aroma/flavor in a smoking material may becontrolled by adjusting concentrations of the solutions or by adjustingspray or coating rates. Process solvents, where they are used, arepreferably evaporated from the smoking material prior to furthertreatment. The advantage of applying the volatile aroma/flavorcomponents before addition of the other components of the smokingmaterials is that good fixation and stabilization results. The volatilesabsorbed onto or into the fibrous structures of the smoking material areeffectively encapsulated by succeeding layers of components depositedupon them.

Propylene glycol, which may be used in the present invention, alsocalled 1,2-propanediol or propane-1,2-diol, is an organic compound (adiol or double alcohol) with formula C3H802. It is a colorless, nearlyodorless, clear, viscous liquid with a faintly sweet taste, hygroscopicand miscible with water, acetone, and chloroform. The commercial productis a racemic mixture. Propylene glycol is considered generallyrecognized as safe (GRAS) by the U.S. Food and Drug Administration, andit is used as an humectant (E1520), solvent, and preservative in foodand for tobacco products, as well as being one of the major ingredientsin “e-liquid” used in electronic cigarettes along with vegetableglycerin. Propylene glycol is also used in the vapor used in vaporizers.

The acute oral toxicity of propylene glycol is very low, and largequantities are required to cause perceptible health damage in humans;propylene glycol is metabolized in the human body into pyruvic acid (anormal part of the glucose-metabolism process, readily converted toenergy), acetic acid (handled by ethanol-metabolism), lactic acid (anormal acid generally abundant during digestion), and propionaldehyde (apotentially hazardous substance). Serious toxicity generally occurs onlyat plasma concentrations over 1 g/L, which requires extremely highintake over a relatively short period of time. It would be nearlyimpossible to reach toxic levels by consuming foods or supplements,which contain at most 1 g/kg of propylene glycol. The potential forlong-term oral toxicity is also low. Because of its low chronic oraltoxicity, propylene glycol was classified by the U. S. Food and DrugAdministration as “generally recognized as safe” (GRAS) for use as adirect food additive.

Glycerol (or glycerine, glycerin) is a simple polyol (sugar alcohol)compound, which may also be employed by the present invention. It is acolorless, odorless, viscous liquid that is widely used inpharmaceutical formulations. Glycerol has three hydroxyl groups that areresponsible for its solubility in water and its hygroscopic nature. Theglycerol backbone is central to all lipids known as triglycerides.Glycerol is sweet-tasting and of low toxicity. In food and beverages,glycerol serves as a humectant, solvent, and sweetener, and may helppreserve foods. It is also used as filler in commercially preparedlow-fat foods (e.g., cookies), and as a thickening agent in liqueurs.Glycerol and water are used to preserve certain types of leaves. As asugar substitute, it has approximately 27 kilocalories per teaspoon(sugar has 20) and is 60% as sweet as sucrose. It does not feed thebacteria that form plaques and cause dental cavities. As a foodadditive, glycerol is labeled as E number E422. It is added to icing(frosting) to prevent it setting too hard.

As used in foods, glycerol is categorized by the American DieteticAssociation as a carbohydrate. The U.S. Food and Drug Administration(FDA) carbohydrate designation includes all caloric macronutrientsexcluding protein and fat. Glycerol has a caloric density similar totable sugar, but a lower glycemic index and different metabolic pathwaywithin the body, so some dietary advocates accept glycerol as asweetener compatible with low carbohydrate diets.

The present invention may modulate nicotinic acetylcholine receptors andother systems that cause nicotine addiction and hence, comprises apotential therapeutic for several nicotine related addictions, symptomsor disorders. In addition to arecoline, other compounds may be employed,such as C-4 substituted; alkyl or aryl substituted; halogenated; C-4 andC-5 substituted halogenated synthetic or imitation nicotine analogs.Many of these novel compounds have demonstrated high receptorselectivity during testing making them good candidates for developmentto replace nicotine in any and all applications that formally containednicotine or in the future might contain nicotine, including but notlimited to, smoking, vaporizing or any application derived from tobacco.

Some of the advantages of the present invention include compounds thathave therapeutic value to help remove withdrawal symptoms from nicotineuse and analogs that have medicinal benefits of nicotine without itsside-effects. The present invention utilizes commercially available andinexpensive raw material, and the process for preparing the analogs isefficient and amenable to large scale production.

The terms “including”, “comprising” and variations thereof mean“including but not limited to”, unless expressly specified otherwise.The enumerated listing of items does not imply that any or all of theitems are mutually exclusive, unless expressly specified otherwise. Theterms “a”, “an” and “the” mean “one or more”, unless expressly specifiedotherwise. None of the description in the present application should beread as implying that any particular element, step, or function is anessential element which must be included in the claim scope. The scopeof the patented subject matter is defined only by the allowed claims.Moreover, none of these claims are intended to invoke paragraph six of35 USC Section 112 unless the exact words “means' for” are followed by aparticiple.

Thus, it is seen that compositions, processes and methods ofmanufacturing synthetic or imitation nicotine are provided. However itis appreciated an understood that the present methods and processes canbe utilized to produce an arecoline final product with uses beyond anicotine substitute, such uses including but not limited to as a naturalbotanical pesticide and fertilizer.

One skilled in the art will appreciate that the present invention can bepracticed by other than the above-described embodiments, which arepresented in this description for purposes of illustration and not oflimitation. The specification and drawings are not intended to limit theexclusionary scope of this patent document. It is noted that variousequivalents for the particular embodiments discussed in this descriptionmay practice the invention as well. That is, while the present inventionhas been described in conjunction with specific embodiments, it isevident that many alternatives, modifications, permutations andvariations will become apparent to those of ordinary skill in the art inlight of the foregoing description.

What is claimed is:
 1. A process of preparing an areca fruit product,the process comprising the steps of: providing a plurality of arecafruits; drying the plurality of areca fruits; dehusking the plurality ofareca fruits to obtain a plurality of areca nuts; chopping, shredding orgrinding the plurality of areca nuts into a multiplicity of areca nutparticles; introducing the multiplicity of areca nut particles into atank containing water at a temperature between 40-90° Centigrade;agitating the multiplicity of areca nut particles to create a slurry;determining an amount of arecoline in the slurry; adding additionalmultiplicities of areca nut particles to the slurry until the slurrycontains a predetermined amount of arecoline; pumping the slurrycontaining the predetermined amount of arecoline through a filter andinto a holding tank; and fermenting said slurry containing thepredetermined amount of arecoline by adding one or more microorganismsto said slurry.
 2. The process of claim 1, further comprising the stepof: before said fermenting step, transferring the slurry from theholding tank into an evaporator and concentrating the arecoline from theslurry in the evaporator.
 3. A process of preparing an areca fruitproduct, the process comprising the steps of: providing a plurality ofareca fruits; drying the plurality of areca fruits; dehusking theplurality of areca fruits to obtain a plurality of areca nuts; chopping,shredding or grinding the plurality of areca nuts into a multiplicity ofareca nut particles; introducing the multiplicity of areca nut particlesinto a tank containing water at a temperature between 40-90° Centigrade;agitating the multiplicity of areca nut particles to create a slurry;determining an amount of arecoline in the slurry; adding additionalmultiplicities of areca nut particles to the slurry until the slurrycontains a predetermined amount of arecoline; pumping the slurrycontaining the predetermined amount of arecoline through a filter andinto a holding tank; and pasteurizing said slurry containing thepredetermined amount of arecoline by first increasing the temperature ofsaid slurry containing the predetermined amount of arecoline and thenrapidly reducing the temperature of said slurry containing thepredetermined amount of arecoline.
 4. The process of claim 3, furthercomprising the step of: before said pasteurizing step, transferring theslurry from the holding tank into an evaporator and concentrating thearecoline from the slurry in the evaporator.
 5. A process of preparingan areca fruit product, the process comprising the steps of: providing aplurality of areca fruits; drying the plurality of areca fruits;dehusking the plurality of areca fruits to obtain a plurality of arecanuts; chopping, shredding or grinding the plurality of areca nuts into amultiplicity of areca nut particles; introducing the multiplicity ofareca nut particles into a tank containing water at a temperaturebetween 40-90° Centigrade; agitating the multiplicity of areca nutparticles to create a slurry; determining an amount of arecoline in theslurry; adding additional multiplicities of areca nut particles to theslurry until the slurry contains a predetermined amount of arecoline;pumping the slurry containing the predetermined amount of arecolinethrough a filter and into a holding tank; transferring the slurry fromthe holding tank into an evaporator; concentrating the arecoline fromthe slurry in the evaporator; and cold pressing said concentratedarecoline to extract said areca fruit product from said concentratedarecoline.
 6. A process of preparing an areca fruit product, the processcomprising the steps of: providing a plurality of areca fruits; dryingthe plurality of areca fruits; dehusking the plurality of areca fruitsto obtain a plurality of areca nuts; chopping, shredding or grinding theplurality of areca nuts into a multiplicity of areca nut particles;introducing the multiplicity of areca nut particles into a tankcontaining water at a temperature between 40-90° Centigrade; agitatingthe multiplicity of areca nut particles to create a slurry; determiningan amount of arecoline in the slurry; adding additional multiplicitiesof areca nut particles to the slurry until the slurry contains apredetermined amount of arecoline; pumping the slurry containing thepredetermined amount of arecoline through a filter and into a holdingtank; and vacuum distilling said slurry containing the predeterminedamount of arecoline.
 7. The process of claim 6, further comprising thestep of: before said vacuum distilling step, transferring the slurryfrom the holding tank into an evaporator and concentrating the arecolinefrom the slurry in the evaporator.